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      Quantitative and pattern recognition analyses of magnoflorine, spinosin, 6′′′-feruloyl spinosin and jujuboside A by HPLC in Zizyphi Semen

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          Abstract

          Two rapid and simple HPLC methods with UV detector to determine three main compounds (magnoflorine, spinosin and 6′′′-feruloyl spinosin) and evaporative light scattering detector (ELSD) to determine jujuboside A were developed for the chemical analyses of Zizyphi Semen. Magnoflorine, spinosin, and 6′′′-feruloyl spinosin were separated with an YMC J’sphere ODS-H80 column (250 mm × 4.6 mm, 4 μm) by the gradient elution followed by the isocratic elution using methanol with 0.1 % formic acid and water with 0.1 % formic acid as the mobile phase. The flow rate was 1.0 mL/min. Jujuboside A was separated by HPLC–ELSD with YoungJinBioChrom Aegispak C18-L column (250 mm × 4.6 mm, 5 μm) column in a gradient elution using methanol with 0.1 % formic acid (A) and water with 0.1 % formic acid as the mobile phase. These two methods were fully validated with respect to linearity, precision, accuracy, stability, and robustness. These HPLC methods were applied successfully to quantify four compounds in a Zizyphi Semen extract. The HPLC analytical methods were validated for pattern recognition analysis by repeated analysis of 91 seed samples corresponding to 48 Zizyphus jujuba var . spinosa (J01–J48) and 43 Zizyphus mauritiana (M01–M43). The results indicate that these methods are suitable for a quality evaluation of Zizyphi Semen.

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          Anxiolytic effect of seed of Ziziphus jujuba in mouse models of anxiety.

          The aim of the present study was to investigate the ethanolic extract of Semen Ziziphi jujuba (SZJE) induced anxiolytic effect. The SZJE was orally administered to male ICR mice, at 0.5, 1.0 and 2. 0 g/kg, 30 min before the behavioral evaluation in the black and white test (BWT) and elevated plus maze (EPM). The SZJE at the dosage 0.5-2.0 g/kg increased the first time entry, total changes and times spent in the white chamber of the BWT. The SZJE at the dosage 0.5-1.0 g/kg increased the percentage of time-spent and the percentage of arm entries in the open arms of the EPM and decreased the percentage of time-spent and the percentage of arm entries in the closed arms of the EPM. Furthermore, the SZJE at the dosage of 1. 0 g/kg prolonged the hexobarbital-induced sleeping time in mice and decreased the locomotor activity in rats. These results suggested that SZJE possessed anxiolytic effect at lower dose and sedative effect at higher dose.
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            Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, on pentobarbital-induced sleep may be related to postsynaptic 5-HT(1A) receptors.

            Previous results have suggested that spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, potentiates pentobarbital-induced sleep via the serotonergic system. The present study investigated whether spinosin potentiates pentobarbital-induced sleep via serotonin-1A (5-hydroxytryptamine, 5-HT(1A)) receptors. The results demonstrated that spinosin significantly augmented pentobarbital (35 mg/kg, i.p.)-induced sleep in rats, reflected by reduced sleep latency and increased total sleep time, non-rapid eye movement (NREM) sleep time, and REM sleep time. With regard to NREM sleep duration, spinosin mainly increased slow-wave sleep (SWS). Additionally, spinosin (15mg/kg, i.g.) significantly antagonized 5-HT(1A) agonist 8-OH-DPAT (0.1mg/kg, i.p.)-induced reductions in total sleep time, NREM sleep, REM sleep, and SWS in pentobarbital-treated rats. These results suggest that spinosin may be an antagonist at postsynaptic 5-HT(1A) receptors because these effects of 8-OH-DPAT were considered to be mediated via postsynaptic 5-HT(1A) receptors. Moreover, co-administration of spinosin and the 5-HT(1A) antagonist 4-iodo-N-{2-[4-(methoxyphenyl)-1-piperazinyl]ethyl}-N-2-pyridinylbenzamide (p-MPPI), at doses that are ineffective when administered alone (spinosin 5mg/kg, p-MPPI 1mg/kg), had significant augmentative effects on pentobarbital-induced sleep, reflected by reduced sleep latency and increased total sleep time, NREM sleep, and REM sleep. In contrast to the attenuating effects of p-MPPI on REM sleep via presynaptic 5-HT(1A) autoreceptors, 15mg/kg spinosin significantly increased REM sleep. These results suggest that the effect of spinosin on REM sleep in pentobarbital-treated rats may be related to postsynaptic 5-HT(1A) receptors.
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              Potential drug targets on insomnia and intervention effects of Jujuboside A through metabolic pathway analysis as revealed by UPLC/ESI-SYNAPT-HDMS coupled with pattern recognition approach.

              Potential metabolites from the metabolic pathways could be therapeutic targets and useful for the discovery of broad spectrum drugs. UPLC/ESI-SYNAPT-HDMS coupled with pattern recognition methods including PCA, PLS-DA, OPLS-DA and Heatmap were integrated to examine the global metabolic signature of insomnia and intervention effects of Jujuboside A (JuA). Six unique pathways of the insomnia were identified using Ingenuity Pathway Analysis (IPA) software. The VIP-value threshold cutoff of the metabolites was set to 10, above this threshold, were filtered out as potential target biomarkers. Sixteen distinct metabolites were identified from these pathways, and 6 of them can be considered for rational drug design. It was further experimental validation that the changes in metabolic profiling were restored to their baseline values after JuA treatment according to the multivariate data analysis. Potential metabolite network of the insomnia was preliminarily predicted JuA-target interaction networks, and could be further explored for in silico docking studies with suitable drugs. Thus, our method is an efficient procedure for drug target identification through metabolic analysis. It can guide testable predictions, provide insights into drug action mechanisms and enable us to increase research productivity toward metabolomic drug discovery. Copyright © 2011 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                +82-53-810-2817 , jkson@yu.ac.kr
                +82-53-850-3620 , +82-53-850-3602 , woomh@cu.ac.kr
                Journal
                Arch Pharm Res
                Arch. Pharm. Res
                Archives of Pharmacal Research
                Pharmaceutical Society of Korea (Heidelberg )
                0253-6269
                1976-3786
                6 December 2013
                6 December 2013
                2014
                : 37
                : 1139-1147
                Affiliations
                [ ]College of Pharmacy, Catholic University of Daegu, Gyeongsan, 712-702 Korea
                [ ]College of Pharmacy, Yeungnam University, Gyeongsan, 712-749 Korea
                [ ]College of Oriental Medicine, Dongguk University, Gyeongju, 780-714 Korea
                Article
                295
                10.1007/s12272-013-0295-z
                4143599
                24310099
                d421c167-ccd6-4053-86ad-fc1d6b4cb90a
                © The Author(s) 2013

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 13 August 2013
                : 10 November 2013
                Categories
                Research Article
                Custom metadata
                © The Pharmaceutical Society of Korea 2014

                6′′′-feruloyl spinosin,jujuboside a,magnoflorine,spinosin,zizyphi semen

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